Association between psoriasis and asthma: a systematic review and bidirectional meta-analysis

Background The risk of asthma in patients with psoriasis has been identified in previous studies, but the bidirectional association between the two has not been fully explored. Methods We thoroughly searched PubMed, Embase, and the Cochrane Library to find relevant observational studies published from the inception of these databases to October 2023. All the risk and bias assessments were analyzed by STATA 16.0. Where the heterogeneity was less than 50%, the fixed effect model was utilized. While where the level of heterogeneity was more than 50%, the random effect model was applied. Moreover, to identify publication bias, a visual funnel chart, and Egger’s test were applied. Results A total of 12,396,911 participants from 16 studies, published between 2011 and 2023 were included in this meta-analysis. We found that psoriasis patients had a higher risk of developing asthma (OR = 1.48, 95%CI 1.28–1.68). Meanwhile, asthma patients also had a higher overall risk of developing psoriasis (OR = 1.33, 95%CI 1.23–1.44). In the subgroup analysis, we found that the type of study, age, and severity of the psoriasis were significant factors in the survey of asthma risk in psoriasis patients. Conclusions In the present systematic review and meta-analysis, we found a bidirectional association between psoriasis and asthma with significantly increased risk. As a result, clinicians should make patients aware of the connection between the two, particularly adolescents or patients with moderate to severe psoriasis who need to be informed about the rising likelihood of developing asthma. Trial registration Registration number CRD42023390111. Supplementary Information The online version contains supplementary material available at 10.1186/s12890-024-03078-7.


Introduction
Psoriasis is a chronic inflammatory skin disease.Its refractory and prone-to-relapse nature has caused considerable concern in the medical world for the past few decades.Erythema and silver scales on the trunk and limbs are its defining features, and its incidence ranges might be as high as 11.43% in the population [1].Psoriasis is considered to be an immune-mediated disease related to IL-23 and IL-17 [2].Psoriasis affects numerous organs and systems, including the cardiovascular system [3], metabolic syndrome [4], kidney disease [5], peripheral vascular disease [6], malignant tumors [7], inflammatory bowel disease [8], and so on, which make it a significant public health issue.Numerous causes intensify the above-mentioned disorders in prediagnosed patients [9].While the introduction of biological agents opens up new possibilities for psoriasis treatment, early detection and intervention remain the most widespread methods of medical care.Therefore, early detection and prevention of psoriasis will benefit from identifying the risk factors associated with the disease's pathogenesis.
Asthma is a chronic, non-infectious disease with airflow obstruction and respiratory symptoms.Antiinflammatory and bronchodilator medications are frequently used to treat asthma to reduce recurrence and regulate symptoms.While around 4.3% of the global population has asthma, its occurrence has been shown to correlate with a country's developmental level, age, gender, and other factors [10].There are well-reported cases of comorbidities, including rhinitis [11], gastroesophageal reflux disease [12], obesity [13], obstructive sleep apnea [14], etc.The connection between skinrelated allergies, asthma, and skin barrier dysfunction has received an increasing focus of attention recently [15,16].However, more research is still needed to confirm the link between psoriasis and asthma.While according to existing literature, asthma is a risk factor for psoriasis [17,18], it has not been investigated whether psoriasis is a risk factor for asthma.
Psoriasis and asthma are both immune-mediated diseases with specific common inflammation-related cytokine-mediated mechanisms.IL-17 should be considered as a biomarker of this phenotype because it has been recently discovered that the differential genes of asthma with high IL-17 expression are the same as those modified in psoriasis [19].This shows that psoriasis and asthma have comparable immunophenotypes.The type 2 IL-17 A pathway [20] has always been an important issue with asthma, particularly in severe cases.Based on the acknowledged role of the IL-17 family in the pathophysiology of psoriasis, asthma and psoriasis may be related.While numerous research has looked at the consequences of psoriasis and asthma, their findings have been unidirectional, with more recent studies looking at the deeper pathophysiological and immunological mechanisms of both conditions.As a result, based on existing research, we hypothesized a bidirectional association between psoriasis and asthma.Thus, we conducted this metaanalysis to evaluate the evidence for a bidirectional connection between psoriasis and asthma.

Materials and methods
We conducted a systematic review and meta-analysis on observational studies (including cohort, case-control, and cross-sectional studies) to explore the bidirectional association between psoriasis and asthma.This systematic review and meta-analysis followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) [21].The protocol was pre-registered in the International Prospective Register of Systematic Reviews (PROSPERO) platform with the registration number CRD42023390111.

Literature search
We searched PubMed, Embase, and the Cochrane Library for relevant studies from the databases' inception to Oct 8th, 2023.The search strategy included medical subject headings (MeSH) and synonyms of psoriasis and asthma.There were no geographic or language restrictions.The search strategy is shown in Supplementary Table 1.

Inclusion criteria and literature screening
The criteria for study selection were: [1] Any Cohort studies, case-control studies, or cross-sectional studies describing the prevalence or risk factors for psoriasis patients with asthma or asthma patients with psoriasis will be included [2].If the case/exposure group is psoriasis patients, the control group comprises people without psoriasis; if the case group is asthma patients, the control group comprises people without asthma [3].Studies of human subjects.Moreover, we excluded duplicate publications, conference abstracts, comments, letters, or studies with irrelevant results.Repeated studies on the same cohort or studies with a sample size of less than 10 were also excluded.
Study selection was performed separately by two authors (XNZ and FW) who also scanned the titles and abstracts independently and obtained the full text of potentially eligible literature.If there was a disagreement between the two authors, let the third author (YPB) make a final decision.

Data extraction
Data extraction was performed independently by two authors (RC and JYL), and the data extraction form was designed in advance according to the guidelines of data extraction of systematic reviews and meta-analysis [22].The baseline form of the included studies contains the first author, year, country, study type, age, follow-up years, diagnostic criteria, number of participants, adjustment, and quality assessment.In case of disagreement, the final decision was made based on a discussion or was resolved by the third author (YPB).

Risk of bias assessment
We used the Newcastle-Ottawa scale (NOS) [23] to assess the quality of cohort studies or case-control studies.NOS scores ranged from 0 to 9, with four stars for participation versus control group selection, two for comparability, and three for outcome assessment and follow-up.Scores of 0-3, 4-6, and 7-9 indicated low, moderate, and high-quality literature, respectively.
As for cross-sectional studies, we used the recommended tools of the Agency for Healthcare Research and Quality (AHRQ) [24].It consists of 11 items, and each item has "yes", "no", and "unclear" responses: "yes" equals 1 point, and "No" or "unclear" equals 0 points.The total score is 11, where 8-11 is high, 4-7 is medium, and 0-3 is low quality.

Statistical analysis
Adjusted ORs and 95% confidence intervals (95% CI) were used to assess data, and I 2 values were used to evaluate heterogeneity among studies within each group analysis.If P > 0.1 and I 2 ≤ 50%, the fixed-effect model was used, and if I 2 > 50% indicated large heterogeneity, the random-effect model was used.When there was too much heterogeneity, a sensitivity analysis was performed, and a recalculation was utilized after excluding the literature with obvious heterogeneity.In order to circumvent publication bias, we observed the funnel plot and used Egger's regression to test the specific value of publication bias.If the result is > 0.05, there is no publication bias, and if it is < 0.05, it will be adjusted following the trimming method.Stata 16.0 (Stata Corp, College Station, Texas) was used for data analysis of the association between psoriasis and asthma.

Quality assessment
The NOS scale and AHRQ were used in this investigation to rate the quality of cohort and cross-sectional studies, respectively.As for the included studies of psoriasis patients with asthma, the NOS scale was used to rate the quality of the cohort studies, which both received scores of 8, and the AHRQ was used to rate the quality of the cross-sectional studies, which received scores ranging from 5 to 9, with an average of 6.9.For the studies about asthma patients with psoriasis, the NOS scale was used to evaluate the quality of four cohort studies, with scores ranging from 7 to 8, with an average score of 7.5.In summary, all studies in this meta-analysis are qualified.The specific scores are shown in Table 1.
Four cohort studies [37][38][39][40] explored the risk of psoriasis in asthmatic patients.According to the meta-analysis, psoriasis was associated with an increased incidence of asthma (OR = 1.331, 95% CI: 1.231-1.440,I 2 = 90.6%,P < 0.01, Fig. 3).However, as the I 2 of the study is higher than 50%, to adjust for heterogeneity, the random effect model is used for analysis.As the sensitivity analysis shows, one article may lead to high heterogeneity so it was excluded from the final results.The adjusted data showed similar results.

Subgroup analysis
We grouped 12 studies according to their type and age, and grouped 10 studies on the severity of psoriasis, focusing on the risk of asthma in patients with psoriasis.However, the risk of psoriasis among patients with asthma could not be analyzed by subgroup because of the small number of included articles.We found that the type of the study, age and severity of psoriasis is affected by asthma.The specific results are shown in Table 2.The risk of asthma in patients with psoriasis was higher in crosssectional studies (OR = 1.489, 95% CI (1.224, 1.811)) than in cohort studies (OR = 1.322, 95% CI (1.235, 1.415)), the risk of asthma was higher in adults (OR = 1.490 95% CI (1.234, 1.799)) than in adolescents (OR = 1.344, 95% CI (1.112, 1.624)), and the risk of asthma was higher in patients with moderate to severe psoriasis (OR = 1.390, 95% CI (1.243, 1.554)) than in patients with mild psoriasis (OR = 1.235, 95% CI (1.072, 1.424)).This shows that there are significant differences between the study type, age, and psoriasis severity groups (p = 0.000).

Publication bias
We tested the publication bias against funnel chart visual examination and Egger's regression test and concluded that there was no significant publication bias in the literature included in the two-way association between psoriasis and asthma (Figs. 4 and 5).The visual results of the funnel chart and the results of two Egger's regression tests (P = 0.708 and P = 0.716) proves that there is no evidence of publication bias.

Main findings
Our meta-analysis investigated the bidirectional association between psoriasis and asthma.This meta-analysis was conducted on 16 studies, including 6 cohort and 10 cross-sectional studies, with a total subject number of 16,657,369.The final results state that asthma increases the risk of psoriasis by 1.48 times, whereas psoriasis increases the risk of asthma by 1.33 times.Concerning the effect of asthma on psoriasis patients, we conducted a  subgroup analysis and found that the different ages, types of research, and severity of psoriasis were affected.

Interpretation of the main results
Asthma increases the chance of developing psoriasis, according to the findings of two previous systematic reviews and meta-analyses [17,18].However, after performing a literature search, we discovered that psoriasis could also act as a risk factor for the development of asthma.As a result, there is an unstudied bidirectional relationship between psoriasis and asthma.To further explore the potential bidirectional relationship between the two, we added additional research to the previous studies that focus on the risk of psoriasis in asthmatic patients.In this systematic review and meta-analysis, we discovered a bidirectional association between asthma and psoriasis acting as mutual risk factors.The co-action mechanism of psoriasis and asthma has attracted scholars' attention in recent years.Traditional T helper cells are subdivided into Th1 and Th2 subgroups due to several cytokines being secreted.Psoriasis is a chronic inflammatory immune-mediated dermatosis that involves both Th1 and Th17 cells, with Th1 cells secreting IFN-γ and TNF-α and Th17 cells secreting IL-17, IL-22 and TNF-α [41].Asthma is thought to be a chronic allergic disease that is mediated by either the Th2 subgroup or a non-Th2 subgroup (Th1 or Th17) [42].However, due to the high degree of heterogeneity among asthmatic patients, the relationship between Th2 and non-Th2 has not been thoroughly elucidated.Among them, Th17 is an important factor related to asthma airway reaction and neutrophil infiltration [43], but its role in asthma is still unclear.In-depth phenotypic studies on asthma patients with high IL-17 expression by certain researchers revealed that this aspect of the phenotype is also present in psoriasis [19], suggesting that IL-17 may act as a link between psoriasis and asthma.
The subgroup analysis further revealed that asthma affected patients with psoriasis differently based on the different ages, severity levels, and study types.Wang [18] conducted a subgroup analysis of age and study type among psoriasis patients, and concluded that older adults were more sensitive to asthma than younger adults.According to Fang et al. [17], there was no difference between the pediatric and adult groups when it came to the increased risk of developing asthma.Interestingly, Fig. 2 Forest plot for studies of the association on psoriasis with asthma our study found that asthma susceptibility was higher in adolescents (≤ 18) (OR = 1.344, 95% CI (1.112,1.624))than in adults (OR = 1.293, 95% CI (1.254,1.332)).However, there were only 3 publications in the adolescent group with moderate heterogeneity (68%), which may impact the finding's accuracy.At the same time, we found that the severity of psoriasis was associated with the susceptibility to asthma to some extent.Among them, severe psoriasis (OR = 1.390, 95% CI (1.243-1.554)) is more susceptible than mild and moderate cases (OR = 1.235, 95% CI (1.072) 1.424).Therefore, the prevalence of asthma in psoriasis should be given more consideration, especially in cases of severe psoriasis.

Implications and limitations
This study is the first to conclusively claim a bidirectional link between psoriasis and asthma, with the systematic review and meta-analysis summarizing all previous  research on the topic.Consequently, this paper proposes that while making a clinical diagnosis, it is essential to consider how psoriasis and asthma differ and interact.Due to the high degree of heterogeneity and the scarcity of studies on psoriasis in asthmatic patients, there are still some limitations to the scope of this study.After performing a sensitivity analysis, the source of the heterogeneity was not identified, and subgroup analysis was not done.With additional literature, the heterogeneity could be decreased in the future.There may be certain issues, such as recall bias since this study is merely a cross-sectional and cohort study focusing on the risk of asthma in psoriasis patients.More diverse types of literature can be utilized to improve the reliability of the findings in subsequent studies.

Conclusions
In conclusion, the evidence in support of a bidirectional relationship between psoriasis and asthma is substantial.The risk of psoriasis in asthma and the risk of asthma in psoriasis are both significant, as shown in this systematic review and meta-analysis.Consequently, patients with asthma should pay attention to the timely identification of psoriatic lesions because, according to the research available at the moment, there are similarities between the two pathogenic mechanisms.Nevertheless, more evidence is still required to support the recommendation that psoriasis patients with respiratory symptoms be tested for asthma.

Fig. 1
Fig. 1 the PRISMA flow chart of study selection

Fig. 3
Fig. 3 Forest plot for studies of the association on asthma with psoriasis

Fig. 4 Fig. 5
Fig. 4 Publication bias of psoriasis patients with asthma

Table 2
Subgroup analysis